Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular structure and conformation of the cis-5,6-dihydrodiol of 7,12-dimethylbenz[a]anthracene has been determined by an X-ray crystallographic analysis. The compound crystallizes in the space group P21/a with cell dimensions a equals 17.799(6), b equals 33.211(8), c equals 5.241(1) A, beta equals 91.88(2)degrees. There are two molecules, designated A and B in the asymmetrical unit, that are not related to each other by crystallographic symmetry. Their conformations are almost identical, and there are no significant differences in their bond lengths or angles. In both molecules the 5-hydroxyl group is equatorial while the 6-hydroxyl group is axial. This conformation is probably forced by steric hindrance between the hydroxyl group, 0-6, and the hydrogen atoms of the 7-methyl group. The molecules pack in the crystal by forming hydrogen bonds between the hydroxyl groups of adjacent molecules, A with A, B, with B, and A with B. The ring system of the cis-5,6-dihydrodiol is much more buckled than is that in 7,12-dimethylbenz[a]anthracene itself. The angle between the two outermost rings is 36 degrees, the deviation from planarity being primarily a consequence of the partial saturation in the ring containing the two hydroxyl groups. Extrapolation of these results to other dihydrodiol derivatives of carcinogenic hydrocarbons permits some predictions of preferred molecular geometry. Thus, the 8,9-dihydrodiol-10,11-epoxide of 7,12-dimethylbenz]a[anthracene, analogous to the biologically active 7,8-dihydrodiol-9,10-epoxide of benzo]a[pyrene, a mutagen that is believed to be an active intermediate in carcinogenesis by benzo]a[pyrene, should probably exist preferentially in a conformation bearing the8-hydroxyl group in the axial orientation.
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PMID:Molecular structure of the K-region cis-dihydrodiol of 7,12-dimethylbenz[a]anthracene. 40 8

Arylhydrocarbon hydroxylase (AHH) activity was determined in cultured human epidermal and dermal cells with and without induction by benz[a]anthracene (BA). Large inter-individual variations were found in the basal and induced AHH activities and the induction ratio. The average basal AHH activity of 29 epidermal cultures in primary culture was 3.9 units (SD, 4.2; range, 0-16.3) (one unit was defined as 1 pmol of 3-hydroxybenzo[a]pyrene formed/mg protein/hr). AHH activity was induced time- and dose-dependently by BA. The average AHH activity induced by treatment with 13 microM BA for 24 hr was 97.4 units (SD, 69.4; range, 2.7-216.9). The induction ratio ranged from 0.6 to 262.0, but in the majority of cultures (15 of 27 cultures, 55%) it was less than 30. The mean induction ratio and SD was 51.1 +/- 63.0. The frequency distributions of basal AHH activity and the induction ratio were asymmetrical with a right tail. No correlation was found between the AHH activity or induction ratio and the age or sex of the donors or their residential district. The basal and induced AHH activities of dermal fibroblasts were both lower than those of epidermal cells; the average basal AHH level of 14 cultures was 1.5 units (SD, 1.4; range, 0-5.2), while the average induced AHH activity was 9.6 units (SD, 6.3; range 0-23.5). The induction ratio of dermal fibroblasts was lower than that of epidermal cells, the mean and SD being 7.5 +/- 7.4 (range, 1.9-27.0). There was no correlation between the AHH activities or induction ratios in epidermal and dermal cells isolated from the same donors.
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PMID:Inter-individual variations of arylhydrocarbon-hydroxylase activity in cultured human epidermal and dermal cells. 310 38

Animal surface temperature profile captured using infrared camera is helpful for the assessment of physiological responses associated with the regulation of body temperature. Diagnosing breast cancer in early stage itself has a greater effect on the prognosis. In this work, asymmetrical temperature distribution analysis of chemical carcinogen 7,12-dimethyl benz(a)anthracene-induced in the lower right flank region of Wistar rats (n = 6) was carried out to test the potential of thermography in diagnosing mammary cancer and tumor growth over a period of nine weeks in comparison with histopathology results as standard. Temperature difference between the tumor induced lower right and left side of flank region was significant (with P value <0.001), whereas in the abdomen and shoulder there was no significant difference in temperature between right and left sides. Percentage of asymmetrical temperature difference in the tumor induced lower flank region was 0.5 to 2%, whereas in the other regions it was <0.5%. Green pixel distribution in RGB color histogram was asymmetrical in the tumor induced lower flank region. Temperature reduction was observed in the tumor induced region after the seventh day of carcinogen induction. Asymmetrical thermogram analysis is the best method of diagnosing mammary cancer and for studying tumor development.
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PMID:Evaluation of mammary cancer in 7,12-dimethylbenz(a)anthracene-induced Wister rats by asymmetrical temperature distribution analysis using thermography: a comparison with serum CEA levels and histopathology. 2309 65

Heparanase has been implicated in cancer but its contribution to the early stages of cancer development is uncertain. In this study, we utilized nontransformed human MCF10A mammary epithelial cells and two genetic mouse models [Hpa-transgenic (Hpa-Tg) and knockout mice] to explore heparanase function at early stages of tumor development. Heparanase overexpression resulted in significantly enlarged asymmetrical acinar structures, indicating increased cell proliferation and decreased organization. This phenotype was enhanced by coexpression of heparanase variants with a mutant H-Ras gene, which was sufficient to enable growth of invasive carcinoma in vivo. These observations were extended in vivo by comparing the response of Hpa-Tg mice to a classical two-stage 12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) protocol for skin carcinogenesis. Hpa-Tg mice overexpressing heparanase were far more sensitive than control mice to DMBA/TPA treatment, exhibiting a 10-fold increase in the number and size of tumor lesions. Conversely, DMBA/TPA-induced tumor formation was greatly attenuated in Hpa-KO mice lacking heparanase, pointing to a critical role of heparanase in skin tumorigenesis. In support of these observations, the heparanase inhibitor PG545 potently suppressed tumor progression in this model system. Taken together, our findings establish that heparanase exerts protumorigenic properties at early stages of tumor initiation, cooperating with Ras to dramatically promote malignant development.
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PMID:Heparanase cooperates with Ras to drive breast and skin tumorigenesis. 2497 Apr 82

The symmetrical and asymmetrical protonation states are realized via the formation of intermolecular hydrogen bonds inside 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene (BP4VA) molecular crystals. With the protonation of H2SO4, BP4VA molecules are protonated symmetrically, while the molecules are asymmetrically protonated by introducing HCl. The different protonation states of BP4VA crystals result in various supramolecular interactions, aggregation states, and even tunable optical properties. It provides a fundamental principle to understand the effect of protonation in organic conjugated molecules and an approach to expanding the scope of organic functional materials.
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PMID:Direct Observation of the Symmetrical and Asymmetrical Protonation States in Molecular Crystals. 2862 50